PT - JOURNAL ARTICLE AU - D.W. Reid AU - C. Ward AU - N. Wang AU - L. Zheng AU - R. Bish AU - B. Orsida AU - E.H. Walters TI - Possible anti-inflammatory effect of salmeterol against interleukin-8 and neutrophil activation in asthma <em>in vivo</em> AID - 10.1183/09031936.03.00109702 DP - 2003 Jun 01 TA - European Respiratory Journal PG - 994--999 VI - 21 IP - 6 4099 - http://erj.ersjournals.com/content/21/6/994.short 4100 - http://erj.ersjournals.com/content/21/6/994.full SO - Eur Respir J2003 Jun 01; 21 AB - In-vitro data suggest that long-acting β2-agonists may have a neutrophil-stabilising effect. A reduction in airway wall eosinophil number following introduction of salmeterol in persistent asthma has previously been described. There is currently interest in the “neutrophil system” in asthma, and thus the aim of the present study was to investigate the effect of salmeterol on interleukin (IL)-8, neutrophils and myeloperoxidase (MPO) in persistent asthma. In the same 12-week double-blind parallel-group placebo-controlled study as described previously, the effects on bronchoalveolar lavage fluid (BALF) IL-8, neutrophils and MPO of introducing salmeterol (50 µg b.i.d.) or giving additional inhaled corticosteroid (fluticasone 100 µg b.i.d.) in 45 subjects with persistent asthma already on low/moderate doses of inhaled corticosteroids were further investigated. At baseline, BALF IL-8 but not neutrophil or MPO levels were significantly raised in the asthmatic subjects compared to normal controls. MPO levels correlated strongly with IL-8 levels, and weakly with BALF neutrophil numbers in the asthmatics. Fluticasone treatment resulted in significantly elevated neutrophil numbers, but not MPO or IL-8 levels. In contrast, introducing salmeterol significantly reduced IL-8 and MPO levels, but did not affect BALF neutrophil numbers. Interestingly, salmeterol and fluticasone showed significantly contrasting effects on MPO and neutrophils, and there was a divergent effect on IL-8 levels that almost reached significance. Excessive interleukin-8 levels may be relevant to asthma pathogenesis, even in the setting of moderate-dose inhaled corticosteroid therapy. Reduction in interleukin-8 production and possibly stabilisation of airway neutrophil numbers may explain the greater clinical benefit of adding a long-acting β2-agonist rather than merely increasing inhaled corticosteroid doses. Indeed, high-dose inhaled corticosteroid therapy alone may promote airway neutrophilia. This study was supported by the National Health and Medical Research Council, (Canberra, Australia), Alfred Hospital Foundation (Melbourne, Australia), Royal Hobart Hospital Research Foundation (Hobart, Australia) and GlaxoSmithKline (Boronia, Australia).